Our objective is directed towards achieving a better understanding of the equilibrium between the tooth and its fluid environment. Such an understanding may lead to the development of a better means of prevention and therapy of dental caries. Our approach involves a multifaceted attack on the problem. The tooth surface/environment fluid equilibrium is studied both in vitro and in vivo. The in vitro studies assess the effects of cyclic systems with phases of de- and remineralization. These phases influence the composition of enamel mineral and, particularly, its resistance to a subsequent acid attack. Single and multiple fluoride treatments have been proven to be protective against acid demineralization. By manipulating the environment, the tooth surfaces become more resistant to acid or caries attack. The in vivo studies are conducted with an intraoral cariogenicity test (ICT) developed for the investigation of caries on sterilized blocks of enamel in the human mouth. Frequent fluoride treatments change the composition of enamel mineral and its resistance to subsequent acid, similar to the effect of the in vitro studies. In the process of intraoral equilibration, salivary organic material is incorporated in presoftened enamel. The nature of this material is similar to that of consolidated lesions and the acquired pellicle. Most likely it is one of the factors responsible for the increased tooth resistance. In other studies we evaluate the response of the ICT plaques to various substrates and fluoride solutions. The essential reactions of the ICT plaques to sugar challenge are similar to those of natural plaques.